Process for preparing cyclicdicarboximido-substituted phosphonothioates

ABSTRACT

Cyclicdicarboximido-substituted phosphonothioates corresponding to the formula WHEREIN R represents phthalimido, monomethyl substituted phthalimido, 4-cyclohexene-1,2-dicarboximido or monomethyl substituted 4-cyclohexene-1,2-dicarboximido are prepared by a method which comprises reacting an appropriate O,O-diloweralkyl phosphorochloridothioate with an appropriate N-alkali metal cyclicdicarboximide reactant in the presence of a catalytic amount of 1,4-diazabicyclo(2,2,2)octane and an inert tertiary alcohol as a reaction medium.

Elnited States Patent [191 t [in 3,853,909

Senkbeil Dec. 10, 1974 [5 PROCESS FOR PREPARING Primary ExaminerAlton D. Rollins CYCLICDICARBOXIMIDO-SUBSTITUTED Assistant ExaminerMark Berch PHOSPHONOTHIOATES Attorney, Agent, or FirmS. Preston Jones [75] Inventor: Herman O. Senkbeil, Midland,

Mich. [57] ABSTRACT [73] Assigneei The Dow Chemical C ompany Cyclicdicarhoximido-substituted phosphonothioates Midland Mich. corresponding to the formula [22] Filed: Apr. 9, 1973 s [21] Appl. No.: 349,154 R-l (loweralkoxy) wherein R represents phthalimido, monomethyl substi- [52] [1.5. Cl 260/326 E tuted phthalimido 4 cyclohexene IZdicarboximido [51 Clor monomethyl substituted 4 cyclohexene l z [58] Fleld of Search 260/326 S, 268 T dicarboximido are prepared by a method which prises reacting an appropriate 0,0-diloweralkyl [56] Referemes C'ted phosphorochloridothioate with an appropriate N- UNITED STATES PATENTS alkali metal cyclicdicarboximide reactant in the pres- 3.321.479 5/l967 Eberhardt 260/268 T ence of a Catalytic amount of 3,647.803 3/1972 Schlottn" 260/268 T diazabicyclo(2,2,2)octane and an inert tertiary alcohol as a reaction medium.

6 Claims, N0 Drawings PROCESS FOR PREPARING CYCLICDICARBOXIMIDO-SUBSTITUTED PHOSPHONOTI-IIOATES BACKGROUND OF THE INVENTION This invention relates to an improved method for preparing cyclicdicarboximido-substituted phosphonothioates corresponding to the general formula (I) wherein in this and succeeding formula, R represents phthalimido monomethyl substituted phthalimido cmQ \N 4-cyclohexenel ,2-dicarboximido and monomethyl substituted 4-cyclohexene-l,2- dicarboximido In the present specification and claims, the term loweralkoxy refers to alkoxy radicals of from 1 to 4 carbon atoms, inclusive. Such radicals would be for example, methoxy, ethoxy, n-propoxy, isopropoxy,. nbutoxy, secondary butoxy and tertiary butoxy. It is to be understood that the two lower alkoxy radicals may be the same or different.

Compounds of the above formula and methods for their preparation as well as a teaching of their utility as pesticides and as active toxicants in compositions for the control of insect, mite, helminth, plant, fungal and bacterial organisms are described in US. Pat. Nos.

is reacted with a cyclicdicarboxylic anhydride of the formula wherein R is hydrogen or a variety of other substituents, in the presence of an inert liquid reaction medium followed by the treatment of the product so produced with a ring-closing reactant such as phosphorus or sulfur based acid halides or an anhydride of an organic mono-, di-, or polycarboxylic acid.

While the above-described processes are effective to produce the compounds they are not entirely satisfactory because of their low yield and new and improved processes are continually being sought.

SUMMARY OF THE INVENTION It has now been found that the cyclicdicarboximidosubstituted phosphonothioates of formula I can be produced in high yields sufficient to warrant economical commercialization and in a novel process by reacting a phosphorochloridothioate of j the formula with an N-alkali metal salt of a cyclicdicarboximide reactant of the formula R NMe or R N-Me 0 ll A wherein R is hydrogen or methyl and Me is sodium or potassium in the presence of a catalytic amount of 1,4- diazabicyclo(2,2,2)octane and a tertiary alcohol as a solvent or reaction medium.

Representative compounds embraced by formula I and which may be prepared by the process disclosed and claimed herein, include:

0,0-dimethyl phthalimidophosphonothioate; O-ethyl O-methyl phthalimidophosphonothioate;

' 0,0-diethyl phthalimidophosphonothioate;

0,0-di-n-butyl phthalimidophosphonothioate; O-ethyl O-isopropyl (4-cyclohexene-l ,2-

dicarboximido)phosphonothioate; 0,0-di-n-propyl phthalimidophosphonothioate; O-secondary-butyl O-methyl phthalimidophosphonothioate; 0,0-di-tertiary-butyl phthalimidophosphonothioate;

O-ethyl O-n-propyl (4-cyclohexene-l ,2-

dicarboximido)phosphonothioate;

O-ethyl O-n-propyl phthalimidophosphonothioate;

0,0-dimethyl (4-methyl-4-cyclohexene-l,2-

dicarboximido)phosphonothioate;

O,-O-di-n-propyl (4-cyclohexene-l,2-

dicarboximido)phosphonothioate;

0,0-dimethyl (4-cyclohexenel ,2-

dicarboximido)phosphonothioate;

0,0-diethyl (4-methylphthalimido)phospho'nothioate;

0,0-di-n-butyl (3-methylphthalimido)phosphonothioate;

0,0-diisopropyl phthalimidophosphonothioate;

0,0-dimethyl (3-methylphthalimido )phosphonothioate; 0,0-dimethyl (4-methylphthalimido)phosphonothioate; 0,0-diethyl (3-methylphthalimido)phosphonothioate;

0,0-diisobutyl phthalimidophosphonothioate;

0,0-dimethyl (3-methyl-4-cyclohexene-l ,2-

dicarboximido)phosphonothioate; and

0,0-diethyl (4-methyl-4-cyclohexene-l ,2-

dicarboximido)phosphonothioate. The critical features of the present process are in the use of l,4-diazabicyclo(2,2,2)octane (also known as triethylenediamine) as a catalyst and in the use of a tertiary alcohol as a solvent or reaction medium. The absence of either of these components drastically reduces the yield of the desired product.

The amount of l,4-diazabicyclo(2,2,2 )octane employed is that amount which allows the compound to act as a catalyst. This compound usually is employed in an amount of from about 0.01 to about 10 mole percent by weight based on the weight of the N-alkali metal cyclicdicarboximide reactant and preferably from about 1 to about 5 mole percent.

While the amount of the co-solvents employed is not critical, it has been found desirable to employ the solvent in an amount of from about 1 up to about or more moles of the tertiary alcohol solvent per mole of the N-alkali metal cyclicdicarboximide reactant. In addition to the use of the tertiary alcohol as a solvent, it has been found that a co-solvent system can be also employed. The cosolvents employed are inert solvents which do not interfere with the action of the catalyst and tertiary alcohol. The specific cosolvent employed is not critical and the only limitation as to the solvent is that it is inertunder the reaction conditions employed. Representative inert co-solvents include hydrocarbons such as, for example, heptane, hexane, benzene, xylene and cyclohexane and halohydrocarbons such as, for example, carbon tetrachloride, chloroform and methylene chloride. When one of the above cosolvents is employed it is usually employed in an amount of from about /2 to about 4 moles of the cosolvent per mole of the tertiary alcohol.

Representative tertiary alcohols useful as the solvent or reaction medium in the present process are the tertiary aliphatic alcohols including for example, tertiarybutyl alcohol, tertiary-amyl alcohol and 3-methyl-3- amyl alcohol; and the tertiary aromatic alcohols such as, for example, triphenyl carbinol.

Representative phosphorochloridothioate reactants include, 0,0-dimethyl phosphorochloridothioate, 0,0- diethyl phosphorochloridothioate, O-secondary butyl O-methyl phosphorochloridothioate, 0,0-di-n-butyl phosphorochloridothioate, 0,0-diisopropyl phosphorochloridothioate, O-ethyl O-methyl phosphorochloridothioate, O-ethyl O-isopropyl phosphorochloridothioate, 0,0-di-n-propyl phosphorochloridothioate, 0,0-ditertiary-butyl phosphorochloridothioate, 0,0-diisobutyl phosphorochloridothioate and O-tertiary-butyl O-n-propyl phosphorochloridothioate.

Representative N-alkali metal cyclicdicarboximide reactants include the N-sodium and potassium derivatives of phthalimide, 3-methylphthalimide, 4- methylphthalimide, 4-cyclohexenel ,2-dicarboximide, 3-methyl-4-cyclohexene-l,Z-dicarboximide, and 4- rnethyl-4-cyclohexene-l ,2-dicarboximide.

The desirable results of the present invention are obtained by reacting the lower alkoxy phosphorochloridothioate reactant and the N-alkali metal cyclicdicarboximide reactant with agitation, in the presence of the tertiary alcohol solvent and 1,4- diazabicyclo(2,2,2)octane catalyst.

Upon completion of the reaction, the desired product can be separated from the reaction mixture by first quenching the reaction mixture, such as, by pouring the reaction mixture into water, adding additional solvent to the mixture followed by heating the mixture from about to about C. The aqueous phase is separated and the organic phase containing the crude product is washed with water and cooled to about 0C. The product is recovered by conventional separatory techniques such as, centrifugation, decantation or solvent evaporation. The product can be further purified, if desired, by solvent recrystallization followed by drying.

If no co-solvent has been employed, the product can be separated by quenching the reaction medium with water and separating the crude product by filtration. The crude product can be further purified by dissolving it in one of the above-identified co-solvents, heating the mixture to reflux followed by the removal of any insoluble material by hot filtration. The solvent crude product mixture is cooled to about 0C. and the product is recovered therefrom by conventional separatory techniques such as, filtration, centrifugation, decantation or solvent evaporation/The product can be further purified, if desired, by solvent recrystallization followed by drying.

lt is to be understood that the specific mode of product separation is not critical and other conventional separatory procedures can be employed.

DESCRlPTlON OF SOME PREFERRED EMBODlMENTS In order that the present invention may be more fully understood, the following examples are given primarily by way of illustration and should not be construed as limitations upon the overall scope of the present invention.

s oar II/ To an agitating mixture comprising 250 pounds (3.37 pound moles) of tertiary-butyl alcohol and 500 pounds (5.80 pound moles) of hexane was added 330 pounds (1.78 pound moles) of potassium phthalimide and 5 pounds (0.045 pound mole; 2.5 mole percent based on potassium phthalimide) 'of 1 ,4- diazabicyclo(2,2,2 )octane. This mixture was heated to 2530C. and thereafter 370 pounds (1.96 pound moles) of 0,0-diethyl phosphonochloridothioate was added over a period of about 2 hours. After a reaction period of 4 hours, the reaction mixture was quenched with water and additional hexane added. The mixture was heated to 6070C. and the aqueous phase re moved. The mixture was water washed for a total of 4 washes and cooled to 0C. The crude 0,0-diethyl phthalimidophosphonothioate product was recovered by centrifugation and the product purified by recrystallization from cold hexane and dried in a vacuum oven at 40C. The product which was recovered in a yield of 75 percent of theoretical, melted at 8l83C. and was about 99 percent pure.

An additional run was carried out as follows:

To an agitating mixture comprising 896 pounds (12.0 pound moles) of tertiary-butyl alcohol and 5 pounds of 1,4-diazabicyclo(2,2,2)octane (0.045 pound mole; 2.5 mole percent based on potassium phthalimide) was added 330 pounds (1.78 pound moles) of potassium phthalimide. This mixture was heated to 2530C. and thereafter 370 pounds (1.96 pound moles) of 0,0- diethyl phosphorochloridothioate was added over a period of about 2 hours. After a reaction period of 4 hours, the reaction mixture was quenched with water and the crude 0,0-diethyl phthalimidophosphonothioate product was recovered by filtration. The product was purified by dissolving it in 1850 pounds of hexane and this mixture was heated to reflux and filtered hot to remove the insoluble by-products which formed. The filtrate was cooled to 0C. and the desired purified product which crystallized upon cooling was recovered by centrifugation. The product was washed with cold hexane and dried in a vacuum oven at 40C. The product was -99 percent pure and was obtained in a yield of 70 percent of theoretical.

Following the general procedure of Example 1, employing 1,4-diazabicyclo(2,2,2)octane as a catalyst and the appropriate N-alkali metal cyclicdicarboximide and 0,0-diloweralkyl phosphorochloridothioate reactants,

the following cyclicdicarboximide phosphonothioates O-ethyl O-methyl phthalimidophosphonothioate having a molecular weight of 285.3 by reacting sodium phthalimide with O-ethyl O-methyl phosphorochloridothioate in the presence of tertiary-butyl alcohol and methylene chloride.

0,0-di-n-butyl phthalimidophosphonothioate having a refractive index N 25/D of 1.5340 and a molecular weight of 355.4 by reacting potassium phthalimide with 0,0-di-n-butyl phosphorochloridothioate in the presence of tertiary-butyl alcohol and xylene.

0,0-diethyl (4-cyclohexenel ,2-dicarboximido) phosphonothioate having a refractive index N 25/D of 1.5205 by reacting the sodium derivative of 4- cyclohexene-l,Z-dicarboximide with 0,0-diethyl phosphorochloridothioate in the presence of tertiarybutyl alcohol.

0,0-di-n-propyl phthalimidophosphonothioate melting at 5253C. by reacting sodium phthalimide with 0,0-di-n-propyl phosphorochloridothioate in the presence of triphenylcarbinol.

0,0-di-n-propyl (4-cyclohexenel ,2-dicarboximido) phosphonothioate having a molecular weight of 331.4 by reacting the potassium derivative of 4-cyclohexene- 1,2-dicarboximide with 0,0-di-n-propyl phosphorochloridothioate in the presence of tertiary-amyl alcohol and cyclohexane.

Following the general procedures outlined above the following additional compounds are prepared.

O-ethyl O-isopropyl (4-cyclohexenel,2- dicarboximido)phosphonothioate having a molecular weight of 317.4;

0,0-diethyl (4-methyl-4-cyclohexene-1,2- dicarboximido)phosphonothioate, an oil having an actual nitrogen content of 4.69 percent compared to a theoretical nitrogen content of 4.42 percent;

- 0,0-dimethyl (4-methyl-4-cyclohexene-1 ,2- dicarboximido)phosphonothioate melting at 4041 5C.;

0,0-dimethyl (4-cyclohexene-1,2-

PREPARATION OF STARTING MATERIALS The N-alkali metal derivatives of the cyclicdicarboximido compounds employed as starting materials can be prepared by known procedures as taught in U.S. Pat.

No. 3,450,713 wherein the cyclicdicarboximido compound of the formula H-R is reacted with an alkali metal hydroxide, and the alkali metal derivative of the dicarboximido compound separated from the reaction mixture.

. wherein R can be prepared by known procedures. For example a thiophosphoryl chloride corresponding to the formula is reacted successfully in either order or simultaneously with a compound having the formula-loweralkoxy-H. Good results are obtained when employing the reactants in amounts which represent equimolecular proportions. When both of the loweralkoxy-H reactants are to be the same, good results are obtained when employing two molecular proportions of such reactant and one molecular proportion of thiophosphoryl chloride.

The reaction is carried out in the presence of an acid binding agent such as, for example, an organic tertiary amine compound. Conveniently the reaction is carried out in an inert organic liquid as reaction medium such as, for example, diethyl ether, benzene, carbon tetrachloride or methylene chloride.

What is claimed is:

I. A process for preparing cyclicdicarboximido phosphonothioates corresponding to the formula represents phthalimido, mono-methyl phthalimido, 4-cyclohexene-l,2-dicarboximido or mono-rnethyl-4-cyclohexenel ,Z-carboximido which comprises reacting a phosphorochloridothioate corresponding to the formula S loweralkoxy (ll-P loweralkoxy with an N-alkali-metal cyclicdicarboximide corresponding to the formula,

' i V Fig NMe or R wherein R represents hydrogen'or methyl and Me represents sodium or potassium at a temperature of from about 0C. to about C. in the presence of acatalytic amount of l,4-diazabicyclo(2,2,2)octane and an inert tertiary alcohol.

2. The process as defined in claim 1 wherein the temperature is in the range of from about 20C. to about 50C., and the inert tertiary alcohol is tertiary-butyl alcoho].

3. The process as defined in claim 2 wherein the cyclicdicarboximido phosphonothioate prepared is 0,0- diethyl phthalimidophosphonothioate.

4. The process as defined in claim 2 wherein the catalyst is present in an amount of from about 0.01 to about 10 mole percent by weight based on the weight of the N-alkali metal cyclodicarboximide reactant.

S. The process as defined in claim 2 wherein the solvent system comprises a mixture of tertiary-butyl alcohol and an inert co-solvent.

6. The process as defined in claim 2 wherein the inert co-solvent is hexane.

@7 3 UNITED STATES PATENT oFFIcE CERTIFICATE @F CORRECTION Patent No- ;853,909 Dated. December 10, l9 74 Inventor(s) Herman 0. Senkbeil It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 2, line 55, the formula should appear as follows:

Column 3, line- 50, change "co-solvents" to solvent Column 8, line 10, the formula should appear as ffollowsz p E/w---Me or Q i p /.N-Me

Signed aridsealed this 11th day of March 1975.

SEAL) ttest:

c. MARSHALL DANN UTH C. MASON Commissioner of Patents rttesting Officer arid Trademarks 

1. A PROCESS FOR PREPARING CYCLICDICARBOXIMIDO PHOSPHONOTHIOATES CORRESPONDING TO THE FORMULA
 2. The process as defined in claim 1 wherein the temperature is in the range of from about 20*C. to about 50*C., and the inert tertiary alcohol is tertiary-butyl alcohol.
 3. The process as defined in claim 2 wherein the cyclicdicarboximido phosphonothioate prepared is O,O-diethyl phthalimidophosphonothioate.
 4. The process as defined in claim 2 wherein the catalyst is present in an amount of from about 0.01 to about 10 mole percent by weight based on the weight of the N-alkali metal cyclodicarboximide reactant.
 5. The process as defined in claim 2 wherein the solvent system comprises a mixture of tertiary-butyl alcohol and an inert co-solvent.
 6. The process as defined in claim 2 wherein the inert co-solvent is hexane. 